Objective: To explore the therapeutic mechanism of Qutan Huoxue decoction in a rat model of non-alcoholic fatty liver disease（NAFLD） based on the insulin receptor substrate（IRS）/phosphatidylinositol 3-kinase（PI3 K）/protein kinase B（AKT）/mammalian target of rapamycin（mTOR） signaling pathway. Methods: Thirty healthy male Sprague-Dawley rats were selected for adaptive feeding for 1 week and randomly divided into normal group（n = 10） and modeling group（n = 20）. The normal group was given normal diet and the modeling group was given high-fat diet for 8 weeks. After the modeling was verified to be successful

the remaining rats in the modeling group（n = 18） were randomly divided into model group（ n = 9） and Qutan Huoxue decoction group（n = 9）. The normal group and the model group were given normal saline by gavage at a dose of 10 mL/（kg·d）

and the Qutan Huoxue decoction group was given intragastric administration of the Qutan Huoxue crude drug at a dose of 11.7 g/（kg·d）. The rats were sacrificed after 4 weeks of intervention. Kits were used to measure serum total cholesterol（TC）

triglyceride（TG）

high-density lipoprotein cholesterol（HDL-C）

low-density lipoprotein cholesterol（LDL-C）

and fasting blood glucose（FBG）. Enzyme-linked immunosorbent assay（ELISA） was used to determine fasting insulin（FINS） and very-low-density-lipoprotein（VLDL） in rats

and to calculate the homeostasis model assessment of insulin resistance（HOMA-IR）. Western blot was used to determine the expression levels of IRS-1

PI3 K

p-PI3 K

AKT

p-AKT

and mTORC1 proteins in liver tissues. Hematoxylin-eosin（HE） staining and oil red O staining were used to observe the morphological changes of liver tissues and the degree of hepatic steatosis in the rats of each group. Results: Compared with the normal group

the model group had significantly higher TC

TG

LDL-C

VLDL

FBG

FINS

and HOMA-IR

as well as expression of IRS-1

p-PI3 K

p-AKT

and mTORC1 proteins in liver tissues

and a significantly lower HDL-C（all P < 0.05）; compared with the model group

the Qutan Huoxue decoction group had significantly lower TC

TG

LDL-C

VLDL

FBG

FINS

and HOMA-IR

as well as expression of IRS-1

p-PI3 K

p-AKT

and mTORC1 proteins in liver tissues

and a significantly higher HDL-C（all P < 0.05）. Compared with the model group

the Qutan Huoxue decoction group had significantly lower degrees of hepatic lipid deposition and hepatic steatosis. Conclusion: Qutan Huoxue decoction can reduce insulin resistance

regulate glucose and lipid metabolism

and reduce hepatic steatosis in NAFLD rats by regulating the IRS/PI3 K/AKT/mTOR signaling pathway.